This project deals with the biological and molecular characterization of murine leukemia viruses (MuLV) with the goal of understanding host and viral factors involved in the pathogenesis of neoplastic and non- neoplastic sequelae of infection. Primary emphasis is on the complex of viruses (LP-BM5 MuLV) responsible for induction of murine AIDS (MAIDS). Infection of sensitive strains of mice with this mixed virus stock, which contains a 4.9kb replication defective genome (BM5def) and B-tropic replication competent ecotropic and MCF helper MuLVs, results in progressive lymphoproliferative disease and immune system impairment and, mostly in mice held long-term, both B and T cell lymphomas can be detected by transfer to Scid mice or, occasionally in situ, by FACS analysis or histopathology. The disease process requires BM5def and both B cells and CD4+ T cells. A BM5def genome containing a viral construct which permits the defective genome and a gene for neomycin resistance to be concordantly expressed has been used to transfect the packaging cell line GP+E-86 to provide a stock of defective, helper-free virus. Although C57BL mice are highly sensitive to development of MAIDS, B6 congenic for the X-linked immunodeficiency (xid) gene are resistant. Uninfected B6.xid mice were found to express high levels of ecotropic MuLV as early as 8 wk of age, much earlier than normal B6. The isolates were B-tropic, in contrast to the usual N-tropism of induced B6 endogenous MuLV sequences. These findings have been extended to BALB.xid, although the frequency of virus expression is much lower, and early expression of virus has been found in Fv-1n C3H.xid. The 2 mechanism of early virus expression and its B-tropism in Fv-1b strains is under study as well as determination of whether the basis for B6.xid resistance to MAIDS is virologic or immunologic.